Hormone Replacement Therapy for Transgenders Do’s and Don'ts

1. Hormone Replacement Therapy for Transgenders Do’s and Don'ts Steven M. Brown, MD University of Wisconsin School of Medicine stevethediseaseslayer@yahoo.com

2. A Case Report

3. What is Hormone Replacement Therapy?

4. What is a Hormone? • Organic compound, secreted by a gland, in minute quantities, into the bloodstream, that has a regulatory effect on the metabolism of tissue or organs at a site different than the site of secretion • Alter the metabolism of cells or the synthesis and secretion of other substances (“tropic hormones”) • Bind to receptors (specific proteins) to “turn on” functions in target tissues

5. Endocrinology 101Glands: Groups of cells which specialize in the secretion of hormones • Some important glands • Pituitary • Anterior pituitary • Growth hormone • Thyroid stimulating hormone • Adrenocorticotropic hormone (ACTH) • FSH • LH • Prolactin

6. Additional glands • Thyroid • Pancreas • Insulin • Hypothalamus • Parathyroid glands • Adrenal glands • Cortisol • Testosterone • Estrogen • Aldosterone

7. The “sex glands” • Ovaries • Progesterone • Estrogen • Regulate reproduction, bone metabolism, regulation of blood cholesterol, breasts, skin • Testes • Testosterone • Regulates reproduction, musculature, bone metabolism, cholesterol levels, red blood cell production

8. Chemical origins of sex hormones • Derived from cholesterol • Chemical structures of estrogen, progesterone, testosterone vary slightly • Testosterone is a metabolite of progesterone • Estrogen is a metabolite of testosterone • Production is governed by negative feedback loops • Present in males and females in differing concentrations

9. Chemical origins of sex hormones

10. Changes which occur in puberty • Pre-wired biological clock, probably in the hypothalamus, coincides with practical reproductive considerations • Hypothalamus releases Leutinising Hormone-Releasing Hormone (LHRH). • LHRH passes down nerve endings, stimulates pituitary gland • In girls, around age 10 to 13, FSH and LH are produced—starts the cyclic activity of the ovaries in the production of estrogen • In boys, ages of 10 and 14 years, FSH and LH “switch on” testicular function in males (FSH triggers sperm production), LH triggers testosterone production

11. Why Use Hormone Replacement? • Change physical appearance to maximize consistency between physical identity and internal gender identity • Assist in “passing” • Create better skin and hair patterns for subsequent cosmetic surgery such as facial feminization • Assist FTM transgenders with “beard growth” • For emotional well-being

12. What are some of the obstacles to HRT? • Patient issues • Ambivalence, “coming out” issues, fears of violence, fears of rejection, discrimination, social stigmatization • Not transsexual or not intensely transsexual • Financial considerations “social and economic marginalization” • Access to health care • Mistrust of medical establishment • Ability to have sustained follow-up and monitoring • Medical/behavioral contraindications • Underlying disease states • Unfavorable family history • Unfavorable lifestyle (tobacco, alcohol)

13. What are some of the obstacles to HRT? • Health care provider issues • Lack of education • Lack of clinical experience • Relative paucity of studies • Unanswered questions • Personal discomfort • Serious complications • Fear of litigation • Off-label administration of medications

14. Who Prescribes Hormone Replacement? • Primary care physician • Internist • Family Practitioner • “Gender dysphoria” clinic • Endocrinologist • Gynecologist • Urologist • SRS Surgeon • Psychiatrists

15. Who SHOULDN’T Prescribe Hormones • Yourself • Family • Friends • Internet “buddies” • “Urgent care” physicians • “On-line” doctors • “On-line” pharmacies

16. Where Transgenders Get Hormones • “Black Market • Friends • Mexico • Internet • Local pharmacy

17. SOME IMPORTANT WARNINGS • NEVER use hormonal medication prescribed for another person • DON’T self-medicate • Use caution in purchasing hormones from “Black market sources”, the Internet, foreign countries, mail order houses and vendors who can “get it or you” • Medication may be impure • May be contaminated • Temptation to bypass appropriate monitoring

18. SOME MORE WARNINGS • Don’t double dose • Don’t alter regimen without supervision

19. An HRT “Do” • A clinician should collaborate with a mental health specialist who has extensive experience with the diagnosis of such patients to avoid mistreatment with hormones or sex-reversing surgical procedures

20. Standards of Care: Harry Benjamin International Gender Dysphoria Association: • Requirements for HRT in adults • Age 18 or older • Demonstrable knowledge of what hormones can and cannot do • Knowledge of social benefits and risks • Documented real-life test for at least 3 months before HRT or • Period of psychotherapy of duration specified by a mental health professional (usually 3 months) • A letter from the mental health professional to the prescribing physician www.hbigda.org.

21. Some important principles • There is a lot of misinformation, especially on the Internet • Hormone therapy remains somewhat “hit and miss” • “Individual results will vary”, especially for MTF • Extremely important to let any treating physician and pharmacist know of all your medications to avoid “drug-drug” interactions and to reduce potential complications • Need to keep spouse/significant others informed

22. Reproductive options • To give opportunity to obtain children who are genetically “their own” • Sperm banking prior to HRT for MTF • FTM’s banking of ovarian tissue or oocytes • Embryo banking Gender reassignment and assisted reproduction, Human Reproduction16: 612-614 (2001)

23. “Real-Life Test” Pros and Cons • Pros • HRT can cause permanent changes including sterility and gynecomastia. RLT may confirm that transitioning is the right choice • Cons • HRT makes it easier to pass and easier to attempt RLT • Most people who would consider hormones are pretty sure of what they want by that time • HRT is “diagnostic” itself—true transsexuals will feel calmer and relieved upon starting HRT; if not truly transsexual, changes will cause worsening anxiety

24. Purposes of Feminizing Hormones • Induce the development of female secondary sexual characteristics • Anti-androgen treatment to reduce the effect of endogenous male sex hormones

25. An important principle—have realistic expectations

26. Feminizing Hormones DO NOT • Cause the voice to increase in pitch. • Dramatically reduce facial hair growth in most people. There are some exceptions with people who have the proper genetic predisposition and/or are less than a decade past puberty. • Change the shape or size of bone structure. However, they may decrease the bone density slightly.

27. Some important DO’s • DO review risks and benefits before starting any hormones • DO be sure that this is what you really, really want…permanent changes can occur within weeks • DO be patient • DO eat healthy and exercise • DO reduce alcohol intake (reduce stress on liver)

28. Some important DO’s • DO have regular medical checkups (every 2-3 months) • DO watch your blood pressure • DO take a good multi-vitamin/mineral supplement to help be sure the body has everything it needs for new development • DO give the body time to adjust • Use the lowest hormone dosage that affords the desired changes. • DO make sure you are not allergic to Provera tablets before you use Depo-Provera sustained release intramuscular injection • DO drink fluids, watch potassium intake if taking spironolactone

29. Some important DO’s of Doctoring • DO see a reputable doctor for your care • DO get regular check-ups • DO be honest and up front with your doctor about all medications • DO make a list of questions prior to each visit—don’t be afraid to ask questions • EDUCATE your doctor, especially if you disagree • DO keep records of all changes—physical and emotional, and SHARE them with your doctors • SEE your doctor for any discharge from breasts

30. Some important DON’TS • DON’T go out on your own for meds • DON’T alter your medication regimen • DON’T BUY hormones on the Internet or through Mexico • DON’T BELIEVE everything you read on the Internet, including web pages, bulletin boards, and chat rooms • DON’T let your weight get out of control • DON’T smoke • DON’T taking the maximum planned dosage of all hormones at once • DON’T take pre-operative dosages of hormones for more than about 3 years

31. Effects of Feminizing Hormones on Males • Effects vary from patient to patient—familial, genetic tendencies • Younger patients generally obtain and more rapid results • Noticeable changes within 2-3 months • Irreversible effects within 6 months • Feminization continues at a decreasing rate for two years or more, often with a “spurt” of breast growth and other changes after orchidectomy

32. Effects of Feminizing Hormones on Males • Breast development • can take years, begins after 2-3 months • final size about 1 to 2 cup sizes less than close female relatives • less satisfactory results in older patients • Only one-third more than a “B”-cup • 45% don’t advance beyond an “A” • growth not always symmetric • Larger male thorax “dilutes” effect • enhanced by progesterone • nipples expand • areolae darken clevelandplasticsurgery.com

33. Effects of Feminizing Hormones on Males • Loss of ability to ejaculate/maintain erection (variable) • Fertility and “male sex drive” drop rapidly—this may become permanent after a few months • Increased female-type sex drive/attraction to men

34. Effects of Feminizing Hormones on Males • Decreased testicular size (mostly flaccid) • The prostate shrinks but does not disappear and prostate cancer is still possible (although risk is reduced) • DO HAVE REGULAR PROSTATE EXAMINATIONS • Decreased penis size, scrotal size (25% within first year), sometimes requiring the patient to stretch by hand to maintain adequate donor material for SRS • Spontaneous erections suppressed within 3 months (but not totally eliminated)

35. Effects of Feminizing Hormones on Males • Decreased facial/body hair • Body hair lightens in texture and color, frequently disappears • Cessation of male pattern baldness • Limited regrowth of scalp hair which has been lost • Improvement in thickness and texture of scalp hair • Enhanced action of 2% or 5% minoxidil (Rogaine®) • Not much effect on distribution of facial hair • Enhanced effect of electrolysis • Decreased rate of growth

36. Cutaneous Effects of Feminizing Hormones on Males • Redistribution of body and facial fat • Face looks more “feminine”—reduced angularity, fuller cheeks • Redistribution of fat from waist to hips and buttocks • Skin softer/smoother/thinner, more translucent, less greasy • Skin sometimes becomes excessively dry • Improvement in spots and acne • Redistribution of fat to hips and buttocks • Brittle fingernails • Increased susceptibility to scratching and bruising • Tactile sensation becomes more intense • Oil and sweat glands become less active, resulting in dryer skin, scalp, and hair

37. Effects of Feminizing Hormones on Males • Sensory changes • Heightened sense of touch • Increased sense of smell • Emotional changes • More labile

38. Effects of HRT on Metabolism in MTF’s • Metabolism decreases • Given a caloric intake and exercise regimen consistent with pre-hormonal treatment • Weight gain • Decreased energy, • Increased need for sleep • Cold intolerance

39. Other effects of hormones • Reduced risk of Alzheimer’s • Improved memory

40. Effects of Feminizing Hormones on Males • Loss of muscle mass • Loss of strength • Estrogen prevents bone loss after testosterone deprivation Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones, Clinical Endocrinology, 48: 347-354

41. Changes in Sexual Orientation “Of 20 transsexuals of various types that were interviewed, 6 heterosexual male-to-female transsexual respondents reported that their sexual orientation had changed since transitioning from male to female…three of the respondents claimed that the use of female hormones played a role in changing their sexual orientation.” Daskalos CT. Changes in the sexual orientation of six heterosexual male-to-female transsexuals. Arch Sex Behav. 1998;27:605-614

42. Risks of Feminizing Hormones —Some General Principles • Complete risks in transsexuals is not known • Most studies are performed in biological women • Limited research regarding risks • Safety data and Food and Drug Administration approval do not acknowledge the use of hormones in transsexuals • All administration is thus “off-label” • Mortality not necessarily increased

43. Risks of Feminizing Hormones • Blood clots— • 12% over age 40 • Usually start in the veins of the legs • Can break off and block blood supply to the lungs—a FATAL complication (pulmonary embolism) • 20-fold increased risk in MTF’s • Risk increased with oral vs. transdermal estrogens • Central retinal vein occlusion has been reported Mortality and morbidity in transsexual subjects treated with cross-sex hormones, Clinical Endocrinology, 47: 37-342 (1997)

44. Surgery Trauma (major or lower extremity) Immobility, paresis Malignancy Cancer therapy (hormonal, chemotherapy, or radiotherapy) Previous venous thromboembolism Increasing age Pregnancy and postpartum period Estrogen therapies Selective estrogen receptor modulators Acute medical illness Heart or respiratory failure Inflammatory bowel disease Nephrotic syndrome Myeloproliferative disorders Paroxysmal nocturnal hemoglobinuria Obesity Central venous catheterization Inherited or acquired thrombophilia Varicose veins Smoking Risk factors for Venous Thromboembolism Risk Factors are Cumulative Geerts et al. CHEST 2004:338S-400S.

45. Reducing the Risk of Blood Clots • Smoking cessation • Pharmacologic support • Relaxation therapy • Behavioral therapy • Discontinue HRT for 3-6 weeks prior to any major surgery, including SRS • Review HRT with surgeon and anesthesiologist prior to minor surgery • Discontinue HRT in injuries which result in immobilization

46. Risks of Feminizing Hormones • Fluid retention • Prolactin • 14%, in one study developed elevations • Pituitary enlargement can sometimes require surgery • Hypertension • May vary with hormone regimen Mortality and morbidity in transsexual subjects treated with cross-sex hormones, Clinical Endocrinology, 47: 37-342 (1997)

47. The Cardiac Risks of Feminizing Hormones • Most studies have and are being done in biologic women • Much evidence suggests that estrogen lowers cholesterol levels, and raises HDL (good cholesterol) • Increases triglycerides, blood pressure, subcutaneous and visceral fat • Decreased LDL particle size (bad) • Decreased insulin sensitivity (bad)

48. Estrogens and the Heart • Current studies • Women’s Health Initiative • 27,500 enrollees without CAD to test estrogen or estrogen plus progestin post-hysterectomy • Women’s Angiographic Vitamin and Estrogen • Women’s Estrogen/Progestin and Lipid Lowering Hormone Atherosclerosis Regression Trial (WELL-HART)

49. Hormones and the Heart • JAMA: July 17, 2002 • “Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women” • 16,608, ages 50-79 studied • Received placebo or Premarin® plus Provera® • Study stopped after 5.2 years because of significantly increased risk of cancer in treatment group • Reduced risk of colorectal cancer and hip fractures • Increased risk of coronary artery disease, pulmonary embolism, stroke

50. Hormones and the Heart • What is the risk-benefit ratio in post-menopausal women? • Decreased hot flashes • How does the risk-benefit ratio differ in transgenders? • Physical feminization • Reduced emotional stress